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Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322
Intracellular differentiation events that determine which cells develop into memory CD8 T cells are currently incompletely understood. Methyl-CpG-binding domain protein 2 (MBD2) is a transcriptional repressor that binds to methylated DNA and mediates the biological consequences of epigenetic gene methylation. The role of MBD2 during the differentiation of naive CD8 T cells into effector and memory cells was determined following acute infection of MBD2-deficient mice with lymphocytic choriomeningitis virus. Despite rapid viral clearance and an efficient primary effector CD8 T cell response, reduced numbers of Ag-specific memory CD8 T cells were observed. Importantly, the appearance of precursor memory cells (IL-7R
high) was delayed. The remaining MBD2–/– memory cells were not fully protective during rechallenge, and memory cell characteristics were altered with regard to surface markers (IL-7R, KLRG-1, CD27, and others) and cytokine production. The defect was CD8 T cell intrinsic, because memory cell development was also delayed when MBD2–/– CD8 T cells were adoptively transferred into SCID mice. These data demonstrate that MBD2 is a previously unrecognized intracellular factor required for the efficient generation of protective memory CD8 T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health primary caretaker technical assistance supplement to Grant 3 U19 AI057266-02S1.
2 Address correspondence and reprint requests to Dr. Ellen N. Kersh, Emory Vaccine Center, Rollins Research Building, Room G211, 1510 Clifton Road, Atlanta, GA 30322. E-mail address: ekersh{at}emory.edu
3 Abbreviations used in this paper: MBD, methyl-CpG-binding domain protein; ko, knockout; LCMV, lymphocytic choriomeningitis virus; p.i., postinfection; MFI, mean fluorescence intensity.
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